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Nature Communications Feb 2024Studying survivorship and causes of death in patients with advanced or metastatic cancer remains an important task. We characterize the causes of death among patients...
Studying survivorship and causes of death in patients with advanced or metastatic cancer remains an important task. We characterize the causes of death among patients with metastatic cancer, across 13 cancer types and 25 non-cancer causes and predict the risk of death after diagnosis from the diagnosed cancer versus other causes (e.g., stroke, heart disease, etc.). Among 1,030,937 US (1992-2019) metastatic cancer survivors, 82.6% of patients (n = 688,529) died due to the diagnosed cancer, while 17.4% (n = 145,006) died of competing causes. Patients with lung, pancreas, esophagus, and stomach tumors are the most likely to die of their metastatic cancer, while those with prostate and breast cancer have the lowest likelihood. The median survival time among patients living with metastases is 10 months; our Fine and Gray competing risk model predicts 1 year survival with area under the receiver operating characteristic curve of 0.754 (95% CI [0.754, 0.754]). Leading non-cancer deaths are heart disease (32.4%), chronic obstructive and pulmonary disease (7.9%), cerebrovascular disease (6.1%), and infection (4.1%).
Topics: Male; Humans; Cause of Death; Breast Neoplasms; Risk Factors; Causality; Heart Diseases
PubMed: 38374318
DOI: 10.1038/s41467-024-45307-x -
The New England Journal of Medicine Aug 2023
Topics: Humans; Adolescent; Diabetes Mellitus, Type 1; Autoimmunity; SARS-CoV-2; COVID-19; Islets of Langerhans; Autoantibodies
PubMed: 37530831
DOI: 10.1056/NEJMc2216477 -
Turk Patoloji Dergisi 2024Epstein-Barr Virus-Associated Smooth Muscle Tumor (EBV-SMT) is a rare tumor with a higher rate of occurrence in unusual locations in the setting of immunodeficiency. In...
OBJECTIVE
Epstein-Barr Virus-Associated Smooth Muscle Tumor (EBV-SMT) is a rare tumor with a higher rate of occurrence in unusual locations in the setting of immunodeficiency. In this study, we evaluated a cohort of ordinary leiomyosarcomas (LMS) for the presence of EBV and described the clinicopathological features deviating from routinely diagnosed cases of EBV-SMT.
MATERIAL AND METHOD
The sections of tissue microarrays including 93 classical LMS occurring in various locations were hybridized with EBER and stained for LMP1 antibody using the Leica Bond Autostainer. EBV real-time PCR assay was performed in 2 EBER-positive cases.
RESULTS
Among the 93 LMS cases, 2 non-uterine cases (2.2%) were positive for EBER and negative for LMP1, and were referred to as `EBV-positive LMS`. Both were females in their 6th decade without immunosuppression. EBV real-time PCR assay revealed the presence of EBV in one of the cases. Tumors were located in the pancreas and chest wall. Morphologically, tumors were rather myxoid, multinodular, and composed of long fascicles of spindle cells with intermediate- to high-grade features. High mitotic activity and focal necrosis were present, whereas no accompanying lymphocytes were detected. One of the patients developed metastatic disease after 3 years.
CONCLUSION
EBV-positive LMS occurring in immunocompetent patients has features distinct from classical EBV-SMT seen in immunosuppressed patients.
Topics: Female; Humans; Male; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Leiomyosarcoma; Smooth Muscle Tumor; Immunocompromised Host
PubMed: 36951222
DOI: 10.5146/tjpath.2023.01600 -
Nature Communications Nov 2023Although the genetic basis and pathogenesis of type 1 diabetes have been studied extensively, how host responses to environmental factors might contribute to...
Although the genetic basis and pathogenesis of type 1 diabetes have been studied extensively, how host responses to environmental factors might contribute to autoantibody development remains largely unknown. Here, we use longitudinal blood transcriptome sequencing data to characterize host responses in children within 12 months prior to the appearance of type 1 diabetes-linked islet autoantibodies, as well as matched control children. We report that children who present with insulin-specific autoantibodies first have distinct transcriptional profiles from those who develop GADA autoantibodies first. In particular, gene dosage-driven expression of GSTM1 is associated with GADA autoantibody positivity. Moreover, compared with controls, we observe increased monocyte and decreased B cell proportions 9-12 months prior to autoantibody positivity, especially in children who developed antibodies against insulin first. Lastly, we show that control children present transcriptional signatures consistent with robust immune responses to enterovirus infection, whereas children who later developed islet autoimmunity do not. These findings highlight distinct immune-related transcriptomic differences between case and control children prior to case progression to islet autoimmunity and uncover deficient antiviral response in children who later develop islet autoimmunity.
Topics: Humans; Child; Autoantibodies; Diabetes Mellitus, Type 1; Transcriptome; Autoimmunity; Insulin; Enterovirus Infections; Islets of Langerhans
PubMed: 37993433
DOI: 10.1038/s41467-023-42763-9 -
MSphere Aug 2023Continued circulation of A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage in poultry has resulted in the diversification in multiple genetic and antigenic...
A Dutch highly pathogenic H5N6 avian influenza virus showed remarkable tropism for extra-respiratory organs and caused severe disease but was not transmissible via air in the ferret model.
Continued circulation of A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage in poultry has resulted in the diversification in multiple genetic and antigenic clades. Since 2009, clade 2.3.4.4 hemagglutinin (HA) containing viruses harboring the internal and neuraminidase (NA) genes of other avian influenza A viruses have been detected. As a result, various HA-NA combinations, such as A/H5N1, A/H5N2, A/H5N3, A/H5N5, A/H5N6, and A/H5N8 have been identified. As of January 2023, 83 humans have been infected with A/H5N6 viruses, thereby posing an apparent risk for public health. Here, as part of a risk assessment, the and characterization of A/H5N6 A/black-headed gull/Netherlands/29/2017 is described. This A/H5N6 virus was not transmitted between ferrets via the air but was of unexpectedly high pathogenicity compared to other described A/H5N6 viruses. The virus replicated and caused severe lesions not only in respiratory tissues but also in multiple extra-respiratory tissues, including brain, liver, pancreas, spleen, lymph nodes, and adrenal gland. Sequence analyses demonstrated that the well-known mammalian adaptation substitution D701N was positively selected in almost all ferrets. In the experiments, no other known viral phenotypic properties associated with mammalian adaptation or increased pathogenicity were identified. The lack of transmission via the air and the absence of mammalian adaptation markers suggest that the public health risk of this virus is low. The high pathogenicity of this virus in ferrets could not be explained by the known mammalian pathogenicity factors and should be further studied. IMPORTANCE Avian influenza A/H5 viruses can cross the species barrier and infect humans. These infections can have a fatal outcome, but fortunately these influenza A/H5 viruses do not spread between humans. However, the extensive circulation and reassortment of A/H5N6 viruses in poultry and wild birds warrant risk assessments of circulating strains. Here an in-depth characterization of the properties of an avian A/H5N6 influenza virus isolated from a black-headed gull in the Netherlands was performed and , in ferrets. The virus was not transmissible via the air but caused severe disease and spread to extra-respiratory organs. Apart from the detection in ferrets of a mutation that increased virus replication, no other mammalian adaptation phenotypes were identified. Our results suggest that the risk of this avian A/H5N6 virus for public health is low. The underlying reasons for the high pathogenicity of this virus are unexplained and should be further studied.
Topics: Humans; Animals; Influenza in Birds; Ferrets; Influenza A Virus, H5N1 Subtype; Influenza A Virus, H5N2 Subtype; Influenza A virus; Poultry
PubMed: 37428085
DOI: 10.1128/msphere.00200-23 -
Revista Do Colegio Brasileiro de... 2023The first cases of the COVID-19 disease were identified in late 2019 in China, but it didnt take long for it to become pandemic. At first, it was believed that it was... (Review)
Review
The first cases of the COVID-19 disease were identified in late 2019 in China, but it didnt take long for it to become pandemic. At first, it was believed that it was restricted to respiratory symptoms only, until extrapulmonary manifestations were reported worldwide. Acute pancreatitis concomitant with the diagnosis of SARS-CoV-2 infection has been observed in some patients, in the absence of the most common etiologies described in the literature. It is postulated that the presence of the ECA-2 viral receptor in the pancreas is responsible for the direct cellular damage and that the hyperinflammatory state of COVID-19 favors the development of pancreatitis through an immune-mediated mechanism. This study aimed to analyze the correlation between acute pancreatitis and COVID-19 disease as a probable causality factor. An integrative literature review was carried out, including studies published between January 2020 and December 2022 that brought data on patients diagnosed with acute pancreatitis according to the revised Atlanta Classification with a confirmed diagnosis of COVID-19 in the same period. A total of thirty studies were reviewed. Demographic, clinical, laboratory and imaging aspects were analyzed and discussed. It is believed that SARS-CoV-2 was responsible for the development of acute pancreatitis in these patients, due to the absence of other precipitating risk factors, as well as the close temporal relationship between both. Attention should be given to gastrointestinal manifestations in patients affected by COVID-19.
Topics: Humans; COVID-19; Pancreatitis; SARS-CoV-2; Acute Disease; Pancreas
PubMed: 37436286
DOI: 10.1590/0100-6991e-20233559-en -
Archives of Pathology & Laboratory... Dec 2023Immunohistochemistry serves as an ancillary diagnostic tool for a wide variety of neoplastic and nonneoplastic disorders, including infections, workup of inflammatory...
CONTEXT.—
Immunohistochemistry serves as an ancillary diagnostic tool for a wide variety of neoplastic and nonneoplastic disorders, including infections, workup of inflammatory conditions, and subtyping neoplasms of the pancreas/liver/gastrointestinal luminal tract. In addition, immunohistochemistry is also used to detect a variety of prognostic and predictive molecular biomarkers for carcinomas of the pancreas, liver, and gastrointestinal luminal tract.
OBJECTIVE.—
To highlight an update on the role of immunohistochemistry in the evaluation of pancreatic/liver/gastrointestinal luminal tract disorders.
DATA SOURCES.—
Literature review and authors' research data and personal practice experience were used.
CONCLUSIONS.—
Immunohistochemistry is a valuable tool, assisting in the diagnosis of problematic tumors and benign lesions of the pancreas, liver, and gastrointestinal luminal tract, and also in the prediction of prognosis and therapeutic response for carcinomas of the pancreas, liver, and gastrointestinal luminal tract.
Topics: Humans; Biomarkers, Tumor; Immunohistochemistry; Liver Neoplasms; Carcinoma; Pancreatic Neoplasms
PubMed: 37134268
DOI: 10.5858/arpa.2022-0462-RA -
BioRxiv : the Preprint Server For... Dec 2023Interleukin-2 (IL-2) variants with increased CD25 dependence that selectively expand Foxp3 regulatory T (T) cells are in clinical trials for treating inflammatory...
Interleukin-2 (IL-2) variants with increased CD25 dependence that selectively expand Foxp3 regulatory T (T) cells are in clinical trials for treating inflammatory diseases. Using an Fc-fused IL-2 mutein (Fc.IL-2 mutein) we developed that prevents diabetes in non-obese diabetic (NOD) mice, we show that Fc.IL-2 mutein induced an activated T population with elevated proliferation, a transcriptional program associated with Stat5- and TCR-dependent gene modules, and high IL-10 and CTLA-4 expression. Increased IL-10 signaling limited surface MHC class II upregulation during conventional dendritic cell (cDC) maturation, while increased CTLA-4-dependent transendocytosis led to the transfer of CD80 and CD86 costimulatory ligands from maturing cDCs to T cells. In NOD mice, Fc.IL-2 mutein treatment promoted the suppression of cDCs in the inflamed pancreas and pancreatic lymph nodes resulting in T cell anergy. Thus, IL-2 mutein-expanded T cells have enhanced functional properties and restrict cDC function, offering promise for targeted immunotherapy use in autoimmune disease.
PubMed: 38106196
DOI: 10.1101/2023.12.01.569613 -
Cancer Immunology, Immunotherapy : CII Dec 2023This study examined the composition of the immune microenvironment at different sites within resected pancreas specimens from patients with pancreatic ductal...
This study examined the composition of the immune microenvironment at different sites within resected pancreas specimens from patients with pancreatic ductal adenocarcinoma (PDAC). Therefore, single-cell suspensions were made from fresh tumor and non-tumorous tissue. Fourteen patients were included from whom twelve PDAC and five non-tumorous samples were obtained. These samples were analyzed with a nineteen marker panel on the Aurora spectral flow cytometer. Furthermore, slides from formalin-fixed paraffine PDACs of eight additional patients were stained with eight markers and analyzed by multispectral imaging. These corresponded to central tumor, periphery of the tumor, i.e., invasive front and resected lymph node and were divided into tumor and adjacent tissue. In the single-cell suspension, a decreased ratio between lymphoid and myeloid cells and between M1 and M2 macrophages was observed in the tumor tissue compared to non-tumorous tissue. Furthermore, an increase in CD169 + macrophages in patients undergoing neoadjuvant therapy was found. Using immunofluorescence, more macrophages compared to T cells were observed, as well as a lower ratio of CD8 to M2 macrophage, a higher ratio of CD4-CD8 T cells and a higher ratio of immune-suppressive cells to pro-inflammatory cells in the PDAC area compared to the adjacent non-tumorous tissue. Finally, there were more immune-suppressive cells in the central tumor area compared to the invasive front. In conclusion, we show a gradient in the immune-suppressive environment in PDAC from most suppressive in the central tumor to least suppressive in distant non-tumorous tissue.
Topics: Humans; Tumor Microenvironment; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Pancreas; T-Lymphocytes
PubMed: 37938368
DOI: 10.1007/s00262-023-03573-6 -
Veterinary Research Dec 2023It is well-established that the genetic diversity, regional prevalence, and broad host range of astroviruses significantly impact the poultry industry. In July 2022, a...
It is well-established that the genetic diversity, regional prevalence, and broad host range of astroviruses significantly impact the poultry industry. In July 2022, a small-scale commercial broiler farm in China reported cases of growth retardation and a 3% mortality rate. From chickens displaying proventriculitis and pancreatitis, three chicken astroviruses (CAstV) isolates were obtained and named SDAU2022-1-3. Complete genomic sequencing and analysis revealed the unique characteristics of these isolates from known CAstV strains in ORF1a, ORF1b, and ORF2 genes, characterized by an unusually high variability. Analysis of amino acid mutations in ORF1a, ORF1b, and ORF2 indicated that the accumulation of these mutations played a pivotal role in the emergence of the variant strain. Inoculation experiments demonstrated that affected chickens exhibited liver and kidney enlargement, localized proventricular hemorrhage, and a dark reddish-brown appearance in about two-thirds of the pancreas. Histopathological examination unveiled hepatic lymphocytic infiltration, renal tubular epithelial cell swelling, along with lymphocytic proventriculitis and pancreatitis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis indicated viremia and viral shedding at 3 days post-infection (dpi). The proventriculus displayed the highest viral loads, followed by the liver, kidney, duodenum, and pancreas. Liver parameters (AST and ALT) and kidney parameters (UA and UN) demonstrated mild damage consistent with earlier findings. While the possibility of new mutations in the ORF2 gene of CAstV causing proventriculitis and pancreatitis warrants further investigation, these findings deepen our comprehension of CAstV's pathogenicity in chickens. Additionally, they serve as valuable references for subsequent research endeavors.
Topics: Animals; Avastrovirus; Chickens; Virulence; Astroviridae Infections; Pancreatitis; Poultry Diseases; Phylogeny
PubMed: 38066626
DOI: 10.1186/s13567-023-01250-1